S H O R T R E P O R T

Eclampsia is more prevalent during the winter seasonin Sweden

A◦

SA RYLANDER1 & PELLE G. LINDQVIST2

1IVF Clinic, Queen Sophia Hospital, Stockholm, and 2Department of Obstetrics and Gynecology, Clintec, KarolinskaUniversity Hospital, Huddinge, Sweden

Key words

Eclampsia, season, sunlight, vitamin D,

incidence, smoking

Correspondence

Pelle G. Lindqvist, Department of Obstetrics

and Gynecology, Clintec, Karolinska University

Hospital, Huddinge, Kvinnokliniken K 57,

SE-14186 Stockholm, Sweden.

E-mail: Pelle.Lindqvist@ki.se

Conflict of interest

The authors have stated explicitly that there

are no conflicts of interest in connection with

this article.

Received: 04 June 2010

Accepted: 21 September 2010

DOI: 10.1111/j.1600-0412.2010.01010.x

Abstract

Hypertensive pregnancy conditions have shown seasonal variations and have been

related to low levels of vitamin D. In Sweden, the hours of sunlight per day are few 

in winter. We hypothesized that eclampsia would be more common in the winter

season. We performed a population-based cross-sectional study of all singleton

deliveries in Sweden during a 5-year period (n = 482,759 women). All parturients

witheclampsia were included as cases andthose without formedcontrol group. The

incidence of eclampsia was nearly doubled during winter season (odds ratio 1.9,

95% confidence interval 1.4–2.6) as compared to other seasons. The incidence of 

eclampsia during the period studied (1990–1994) was four in 10,000 pregnancies.

We found that eclampsia was twice as common in winter and we introduce the

alternative hypothesisthat lackof sunlight exposureincreases women’s susceptibility 

to eclampsia, possibly due to vitamin D insufficiency.

Introduction

Eclampsia is a maternal complication of preeclampsia occur-

ring in two to ten of 10,000 pregnancies. It is related to both

fetal and maternal morbidity and mortality. There are many 

epidemiological reports of different incidences of eclamp-

sia depending on season (for references) (1). Environmental

factors, such as low temperature, high humidity/rainy season

and reduced barometric pressure have been suggested to be

related to an increased risk, but results are not consistent (1).

Preeclampsia has also been related to an increased inflamma-

tory response with increased levels of IL-6, IL-8 and TNFα,

and lower levels of modulator cytokines such as IL-10 (2).

Regarding eclampsia, presumably the time span in close re-

lation to delivery is most important for triggering seizures.

Therefore, in this study, we focus on eclampsia.

Low maternal vitamin D level in both early and late preg-

nancy has been related to preeclampsia (3). The major source

of vitamin D is sunlight ultraviolet B radiation (wavelength

between 290 and 315 nm), which converts previtamin D to

vitamin D. In the Nordic countries, the levels of vitamin D

vary widely with season, with normal levels during summer

and low or subnormal levels during winter (4,5). The hy-

droxylation of 25-OHVitD into its active form 1α,25(OH)2

vitamin D3 (1,25VitD) takes place in a number of systems,

such as the endothelium, intestines and brain, but mainly in

the kidney (5).

Whether eclampsia is related to the amount of sunlight,

however, is unknown. We hypothesized that eclampsia would

be more common in the winter season in Sweden, when the

hours of sunlight are few.

Material and methods

This study is an analysis comprising all singleton pregnan-

cies recorded at the National Birth Registry of Sweden over a

5-year period (1990–1994) (n = 482,759). All singleton par-

turients with eclampsia were included as cases; and those

without eclampsia formed a control group. The diagno-

sis of eclampsia was that which was obtained from the

National Birth Registry. Preeclampsia was defined as

pregnancy-induced hypertension (≥140/90 mmHg) and

114c 2010 The Authors

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A◦

. Rylander and P. G. Lindqvist Eclampsia and season

proteinuria ≥0.3 g/l. Eclampsia was defined as preeclamp-

sia in combination with general convulsions.

Season of birth was categorized into: winter (December to

February), spring (March to May), summer (June to August)

or autumn (September to November). Because odds ratios

(ORs) were similar in analysis of eclampsia, season was di-

chotomized into winter or other seasons (reference). Parity 

was classified as nulli- (no previous birth) or multiparous

(at least one previous birth= reference). Smokers were char-

acterized by daily cigarette consumption into smokers or 0

(non-smokers or occasional smokers = reference). Maternal

age was classified as either ≤34 years (reference), or≥35. Re-

gion of the country was categorized into north, middle and

south.

ORs were determined with multiple logistic regression

analysisof theoutcome variable eclampsia compared to com-

binations of the independent (explanatory) variables season,

smoking, maternal age, parity, region and fetal gender. Cross-

tabulations with the chi-squared test were used for bivariate

analysis. By using 0.05 two-sided significance level and in-

cluding 480,000 women, assuming the incidence of eclamp-

sia to be 4/10,000, we would have 70% power to identify a

50% increased risk during winter season. We did not include

missing data in the analysis. The Statistical Package for the

Social Sciences (SPSS Inc., Chicago, IL, USA) software was

used. p -Values less than 0.05 were considered significant.

Results

The results of bivariate and multivariate analysis of eclampsia

are presented in Table 1. The incidence of eclampsia was

nearly doubled during the winter season as compared to

other seasons. Smoking lowered the risk by 40% (OR 0.6,

95% CI 0.4–0.9), while nulliparous women were at a four-

fold increased risk (OR 3.6, 95% CI 2.5–5.2). High maternal

age (≥35) was related to a 60% increased risk (OR 1.6, 95%

CI 1.03–2.6). There were no differences depending on part

of the country. The number of sun-hours per day and the

number of eclampsia cases per 10,000 deliveries are shown in

Figure 1.

Discussion

In this study, we found the risk of eclampsia being almost

doubled during winter season as compared to other seasons.

There was no difference between north and south Sweden

regarding eclampsia. Our finding gives epidemiological sup-

port for the hypothesis that lack of sunlight exposure and

vitamin D insufficiency is involved in the pathogenesis of 

eclampsia. However, our findings may only be hypothesis

generating.

The large population-based study design is a strength of 

the present study. However, the retrospective designmay have

introduced biases. If some eclampsia cases were missed, it

would only have had a minor effect on the risk estimates

and the incidence in our material was similar to that usu-

ally reported for the period (4/10,000 pregnancies). These

results may only be valid in countries with large differences

in the amount of sunlight between seasons, that is at high

latitudes and in populations with subnormal vitamin D lev-

els. Swedes in general have a sun-seeking behavior. The daily 

exposure to ultraviolet radiation (sun exposure) has been

shown to influence the vitamin D status (4). We recognize

it as a limitation that we have only data on the amount

of sun in relation to season, and not personal data on sun

habits. Several other climatic/environmental factors, which

Table 1. Risk of eclampsia in relation to season and part of the country.

Eclampsia∗ Control group∗ Bivariate analysis Multivariate analysis∗∗

(n = 182) (n = 482,477) OR 95% CI OR 95% CI

Season

Spring 43 133,576 1.1 0.7–1.7 1.1 0.7–1.7

Summer 36 123,500 1.0 Reference 1.0 Reference

Fall 36 109,712 1.1 0.7–1.8 1.1 0.6–1.7

Winter 67 115,666 2.0 1.3–3.0 1.9 1.3–3.0

Winter season

Yes 67 115,666 1.8 1.4–2.5 1.9 1.4–2.6

No 115 366,811 1.0 Reference 1.0 Reference

Part of the country

South 68 176,378 1.0 Reference 1.0 Reference

Middle 82 225,416 0.9 0.7–1.3 0.9 0.6–1.3

North 32 80,599 1.0 0.7–1.6 1.0 0.7–1.6

OR = odds ratio, 95% CI = 95% confidence interval.∗We give the total numbers and the number with data present. Those with missing data were not included.∗∗Adjustment in multivariate analysis: smoking, fetal gender, parity and age groups.

c 2010 The Authors

 Acta Obstetricia et Gynecologica Scandinavica c 2010 Nordic Federation of Societies of Obstetrics and Gynecology 90 (2011) 114–117 115

 

Eclampsia and season A◦

. Rylander and P. G. Lindqvist

Figure 1. Mean number of daily hours of sunlight and incidence of eclampsia per 10,000 deliveries.

have not been adjusted for might confound the results, such

as humidity, altitude, physical activity, infections, nutritional

factors and social behavior. Our hypothesis is not in opposi-

tion to the theory of seasonal variation (with increased risk 

in cold and humid/rainy weather) (1) or the results of risk 

reduction of eclampsia with calcium supplementation (6).

Lack of sunlight will result in colder weather and also an

impaired calcium metabolism. In addition, our hypothesis is

in agreement with the shown fibrinolytic and the cytokine

changes in severe preeclampsia (2,7,8).

Eclampsia has generally been described as an endothe-

lial disease. The tissue plasminogen activator antigen (tPA

Ag) level is useful as a marker of endothelial dysfunction,

and levels of 25-OHVitD have been shown to be inversely 

related to tPA Ag levels in vivo (8). The tPA level is also re-

lated to preeclampsia (8). Endothelial cells show 1,25VitD

receptor activity together with a 1α-hydroxylas enzyme for

local 1,25vitD production from 25-OHVitD. Supplementing

patients with Type 2 diabetes mellitus and low 25-OHVitD

status with vitamin D, improves endothelial function (9). It

has been estimated that among those living at high latitudes

almostno vitaminD is producedin winterfromsunlight (10).

Since both food and food supplements are generally low in

vitamin D, a large proportion of the childbearing population

may also be affected by an insufficient vitamin D status in

winter (4).

There are several possible mechanisms by which the win-

ter season may have doubled the risk of eclampsia. It may 

be caused by (a) increased blood pressure (5), (b) increased

vascular resistance (5), (c) excessive expression of inflamma-

torycytokines(TNFα, IL6) andby decreasing IL10 (5). Thus,

we speculate that less sun exposure during winter season will

provoke vitamin D insufficiency, which is more unfavorable

for a normal pregnancy. There are several epidemiological

data indicating that preeclampsia is related to low vitamin D

levels. Our epidemiological study cannot rule out cold as the

predisposing condition. There was, however, no difference

between north and south Sweden regarding risk of eclamp-

sia. Other possible causes are infections or other nutritional

factors that differ between seasons.

Insufficiency or deficiencyof vitaminD willcause parathy-

roid hormones to rise, leading to hypocalciuria. A thorough,

large-scale study in the USA did not find any difference

in urinary calcium levels between normal and preeclamp-

tic women (6). This might be explained by adequate food

and sun exposure habits in north America. Recently, women

taking multivitamin preparationsupon conceptionhavebeen

shown to be at lower risk of preeclampsia, fetal growth re-

striction and preterm birth (11). However, the authors of 

those studies mainly considered the vitamin E and folic acid

supplementation. Supplementation with vitamin D has been

reported to lower theriskof preeclampsia (12). A randomized

116c 2010 The Authors

 Acta Obstetricia et Gynecologica Scandinavica c 2010 Nordic Federation of Societies of Obstetrics and Gynecology 90 (2011) 114–117

 

A◦

. Rylander and P. G. Lindqvist Eclampsia and season

controlled trial of vitamin D supplementation may separate

the effects of sun exposure and cold as predisposing mech-

anisms. If the patophysiological mechanisms of eclampsia

could be determined better, it would have a large impact on

surveillance of women at risk.

As eclampsia wastwice as commonin winter, we introduce

the alternative hypothesis that lack of sunlight exposure in-

creases women’s susceptibility to eclampsia, possibly due to

vitamin D insufficiency.

Funding

No specific funding.

Acknowledgements

We acknowledge the help provided by the National Board of 

Health and Welfare in extracting data from theNational Birth

Registry. The study was supported by Karolinska University 

Hospital, Huddinge, Karolinska Institute fund, and Queen

Sophia Hospital, Stockholm.

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c 2010 The Authors

 Acta Obstetricia et Gynecologica Scandinavica c 2010 Nordic Federation of Societies of Obstetrics and Gynecology 90 (2011) 114–117 117